Supplementation of VigantOL® Oil Versus Placebo as Add-on in Patients With Relapsing Remitting Multiple Sclerosis Receiving Rebif® Treatment

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— SOLAR  

Official title:

A Three Arm, Randomized, Double Blind, Placebo Controlled, Multicenter, Phase II Study to Evaluate the Efficacy of Vigantol® Oil as Add on Therapy in Subjects With Relapsing Remitting Multiple Sclerosis Receiving Treatment With 44mg Tiw of Rebif®

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01285401
• Other study ID #: EMR 200136-532
• Secondary ID: 2010-020328-23
• Status: Completed
• Phase: Phase 2
• First received: January 26, 2011
• Last updated: June 3, 2015
• Start date: March 2011
• Est. completion date: April 2015

Study information

• Verified date: June 2015
• Source: Merck KGaA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Agency for Health and Food SafetyBelgium: Ministry of Social Affairs, Public Health and the EnvironmentDenmark: Danish Medicines AgencyEstonia: The State Agency of MedicineFinland: Finnish Medicines AgencyGermany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencyLatvia: State Agency of MedicinesLithuania: State Medicine Control Agency - Ministry of HealthNetherlands: Medicines Evaluation Board (MEB)Norway: Norwegian Medicines AgencySwitzerland: Swissmedic
• Study type: Interventional

Clinical Trial Summary

The drug being tested is called VigantOL® oil - a very effective form of Vitamin D hormone supplement (cholecalciferol). Low levels of Vitamin D have been described to be associated with a higher risk of developing Multiple Sclerosis (MS), and it is known that up to 90% of patients with Multiple Sclerosis have Vitamin D deficiency.

Rebif® is known to be an effective treatment for slowing down the progression of MS. The purpose of this research trial is to evaluate if VigantOL® oil on top of Rebif® has any benefit on the progression of MS compared to Rebif® and placebo.

Disease activity will be assessed by clinical examination and Magnetic Resonance Imaging (MRI). The planned study treatment duration for each study participant is 48 weeks, and the study consists of a total of 8 visits. Study participants who are already passed Week 48 at the time of approval of Protocol Amendment 5 will have a study duration of 96 weeks and a total of 12 visits.

During the study, the participant will undergo physical examination, neurological assessments, safety assessments, blood tests and urinalysis (including pregnancy tests).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 232
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Diagnosis of a relapsing-remitting form of MS

• Brain and/or spinal MRI with findings typical of MS

• A first clinical event prior to Screening.

• Disease activity

• EDSS score of less than, or equal to 4.0 at Screening.

• Currently treated with interferon-beta-1a 44mg (tiw) sc

• Willingness and ability to comply with the protocol

• Written informed consent

Exclusion Criteria:

• Pregnancy and lactation period

• Any disease other than MS that could better explain signs and symptoms.

• Complete transverse myelitis or bilateral optic neuritis.

• Currently receiving or use at any time of monoclonal antibodies, mitoxantrone, cytotoxic or immunosuppressive therapy (excluding systemic steroids and adrenocorticotrophic hormone [ACTH]), B cell modulating therapies (e.g. RituxiMab or BelimuMab), total lymphoid irradiation or bone marrow transplantation.

• Use of any cytokine other than interferon or anti-cytokine therapy, intravenous immunoglobulin, plasmapheresis, or any investigational drug or experimental procedure

• Use of oral or systemic corticosteroids or ACTH

• Have abnormalities of Vitamin D related hormonal system other than low dietary intake or decreased sun exposure, i.e. primary hyperparathyroidism or granulomatous disorders.

• Have an urine calcium/creatinine (mmol/mmol) ratio greater than 1.0 or hypercalcaemia

• Are taking medications that influence Vitamin D metabolism other than corticosteroids, e.g., phenytoin, barbiturates, thiazide diuretics and cardiac glycosides.

• Are taking more than 1000 IU (25 µg) of Vitamin D supplement daily.

• Have conditions with increased susceptibility to hypercalcaemia, e.g., known arrhythmia or heart disease, treatment with Digitalis, or Hydrochlorothiazide and those who suffer from nephrolithiasis.

• Have inadequate liver function

• Moderate to severe renal impairment

• Inadequate bone marrow reserve

• History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (NYHA class 3 or 4).

• History or presence of severe depression, history of suicide attempt, or current suicidal ideation.

• Epilepsy or seizures not adequately controlled by treatment.

• Current or past alcohol or drug abuse.

• Any major medical or psychiatric illness (such as psychosis, bipolar disorder) that in the opinion of the Investigator could create undue risk to the subject or could affect adherence with the trial protocol.

• Known contra-indication to treatment with vitamin D

• Known hypersensitivity to interferon or its excipient(s)

• Known hypersensitivity to gadolinium.

• Any other condition that would prevent the subject from undergoing an MRI scan.

• Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

• Positive HIV, hepatitis C, or hepatitis B (HBsAg and HBc antibody) serology (test performed at screening).

• Legal incapacity or limited legal capacity.

• Another current autoimmune disease, except diabetes.

• Have experienced a relapse within 30 days.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• VigantOL® oil plus interferon beta-1a (Rebif®)
VigantOL® oil 6,670 International Units/day (IU/d) (167 microgram per day [mcg/day]), orally administered for 4 weeks followed by 14,007 IU/d (350 mcg/d) orally administered for 44 weeks on top of Rebif® 44mcg three times per week (tiw) administered sub-cutaneously. Subjects who have already passed Week 48 at the time of approval of Protocol Amendment 5 in their country will be receive 14,007 IU/d (350 mcg/d) orally administered for 92 weeks.
• Placebo plus interferon beta-1a (Rebif®)
Matching placebo daily, orally administered plus Rebif® 44 mcg tiw, sub-cutaneously.

Biological:
• Interferon beta-1a (Rebif®) alone
Rebif® 44 mcg tiw, sub-cutaneously alone.

Locations

Country	Name	City	State
Austria	Research Site	Vienna
Denmark	Research Site	Esbjerg
Denmark	Research Site	Glostrup
Denmark	Research Site	Sønderborg
Denmark	Research Site	Vejle
Denmark	Research Site	Viborg
Estonia	Research Site	Tallinn
Finland	Research Site	Helsinki
Finland	Research Site	Turku
Germany	Research Site	Bad Neustadt / Saale
Germany	Research Site	Bamberg
Germany	Research Site	Berlin
Germany	Research Site	Erlangen
Germany	Research Site	Freiburg
Germany	Research Site	Hannover
Germany	Research Site	Köln
Germany	Research Site	Münster
Germany	Research Site	Regensburg
Germany	Research Site	Rostock
Italy	Research Site	Cefalu
Latvia	Research Site	Riga
Lithuania	Research Site	Kaunas
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Gouda
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Rotterdam
Netherlands	Research Site	Sittard
Norway	Research Site	Bergen
Norway	Research Site	Lørenskog
Norway	Research Site	Tromsø
Portugal	Research Site	Amadora
Portugal	Research Site	Lisboa
Portugal	Research Site	Porto
Switzerland	Research Site	Bern
Switzerland	Research Site	Lausanne
Switzerland	Research Site	Lugano
Switzerland	Research Site	St. Gallen
Switzerland	Research Site	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
Merck KGaA

Countries where clinical trial is conducted

Austria,  Denmark,  Estonia,  Finland,  Germany,  Italy,  Latvia,  Lithuania,  Netherlands,  Norway,  Portugal,  Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of subjects with disease activity free status (no relapses, no EDSS progression and no new Gd-enhancing or T2 MRI lesions) at Week 48		48 weeks	No
Secondary	Percentage of relapse-free subjects at Week 48		48 Weeks	No
Secondary	Percentage of subjects free from any Expanded Disability Status Scale (EDSS) progression at Week 48		48 Weeks	No
Secondary	Time to confirmed EDSS progression		48 Weeks	No
Secondary	Percentage of subjects free from confirmed EDSS progression at Week 48		48 Weeks	No
Secondary	Cumulative number of T1 gadolinium enhancing lesions at Week 48		48 Weeks	No
Secondary	Mean number of combined unique active (CUA) lesions per subject per scan at Week 48		48 Weeks	No
Secondary	Cumulative number of new combined unique active (CUA) lesions at Week 48		48 Weeks	No
Secondary	Mean change from baseline in the total volume of T2 lesions at Week 48 (T2 Burden of disease)	Total volume of T2 lesions will be assessed in mm^3	Baseline and 48 Weeks	No
Secondary	Percentage of subjects free from T1 gadolinium enhancing lesions at Week 48		48 Weeks	No
Secondary	Percentage of subjects free from new T1 hypointense lesions (black holes) at Week 48		48 Weeks	No
Secondary	Percentage of new T1 hypointense lesions (black holes) at Week 48 within the subgroup of new or enlarging non-enhancing T2 lesions		48 Weeks	No
Secondary	Time to first documented relapse		48 weeks	No
Secondary	Annualised relapse rate at Week 48		48 weeks	No
Secondary	Total number of reported relapses at all time points up to 48 weeks		up to 48 weeks	No
Secondary	Percentage of subjects treated with glucocorticoids due to relapses		48 weeks	No
Secondary	Mean change from baseline in the total volume of T1 hypointense lesions at Week 48		Baseline and 48 Weeks	No